Fig. 33.2 ), with approximately 10 superficial nephrons for each juxtamedullary nephron. The 585 • Fig. 33.3 Diagram of a nephron including cellular ultrastructure. Inner medulla collecting duct Ascending thin limbThick ascending limb Descending thin limb Proximal tubule Macula densa Cortical collecting duct Distal tubule Principal cell Intercalated cell OutermedullaInner medulla Cortex • Fig. 33.4 Scanning electron micrograph illustrating primary cilia (C, ≈2 to 30 µm long and 0.5 µm in diameter) in the apical plasma membrane of principal cells in the cortical collecting duct. Note that intercalated cells (IC1 and IC2) do not have cilia but have numerous microvilli. CD, collecting duct principal cells with short microvilli (arrowhead); straight ridges (open arrow) represent the cell borders between principal cells; IC1 and IC2, intercalated cells with numerous long microvilli in the apical membrane. (From Kriz W, Kaissling B. Structural organization of the mammalian kidney. In: Seldin DW, Giebisch G [eds]. The Kidney: Physiology and Pathophysiology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2000.) glomerulus of each superficial nephron is located in the outer region of the cortex. The corresponding loops of Henle are short, and associated efferent arterioles branch into peritubular capillaries that surround its associated nephron segments as well as adjacent nephrons. This capillary network conveys oxygen and important nutrients to the nephron segments in the cortex, delivers substances to individual nephron segments for secretion (i.e., movement of a substance from blood into tubular fluid), and serves as a pathway for return of reabsorbed water and solutes to the circulatory system. A few species, including humans,
Polycystin 1 (encoded by the PKD1 gene) and polycystin 2 (encoded by the PKD2 gene) are expressed in the membrane of primary cilia and mediate entry of Ca++ into cells. PKD1 and PKD2 are thought to play an important role in flow-dependent K+ secretion by principal cells of the collecting duct. As described in more detail in
Chapter 36, increased flow of tubule fluid in the collecting duct is a strong stimulus for secretion of K+ . Increased flow bends the primary cilium in principal cells, which activates the PKD1/PKD2 Ca++-conducting channel complex and allows Ca++ to enter the cell and increase intracellular [Ca++]. The increase in [Ca++] activates K+ channels in the apical plasma membrane, which enhances secretion of K+ from the cell into the tubule fluid.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, occurring in about 1 in 1000 people. Approximately 12.5 million people worldwide have ADPKD, which is caused primarily by mutations in PKD1 (85%–90% of cases) or PKD2 (≈15% of cases). The major phenotype of ADPKD is enlargement of the kidneys due to the presence of hundreds or thousands of space-occupying renal cysts that can be as large as 20 cm in diameter. Cysts are also seen in the liver and other organs in this condition. About 50% of patients with ADPKD progress to renal failure by the age of 60. Although it is not clear how mutations in PKD1 and PKD2 cause ADPKD, renal cyst formation may result from defects in Ca++ uptake that alter Ca++-dependent signaling pathways, including those controlling kidney cell proliferation, differentiation, and apoptosis.
also possess very short superficial nephrons whose loops of Henle never enter the medulla.
The glomerulus of each juxtamedullary nephron is located in the region of the cortex adjacent to the medulla (see